Abstract:
:DNA wrapping around histone octamers generates nucleosomes, the basic compaction unit of eukaryotic chromatin. Nucleosome stability is carefully tuned to maintain DNA accessibility in transcription, replication, and repair. Using freely orbiting magnetic tweezers, which measure the twist and length of single DNA molecules, we monitor the real-time loading of tetramers or complete histone octamers onto DNA by Nucleosome Assembly Protein-1 (NAP1). Remarkably, we find that tetrasomes exhibit spontaneous flipping between a preferentially occupied left-handed state (ΔLk = -0.73) and a right-handed state (ΔLk = +1.0), separated by a free energy difference of 2.3 kBT (1.5 kcal/mol). This flipping occurs without concomitant changes in DNA end-to-end length. The application of weak positive torque converts left-handed tetrasomes into right-handed tetrasomes, whereas nucleosomes display more gradual conformational changes. Our findings reveal unexpected dynamical rearrangements of the nucleosomal structure, suggesting that chromatin can serve as a "twist reservoir," offering a mechanistic explanation for the regulation of DNA supercoiling in chromatin.
journal_name
Cell Repjournal_title
Cell reportsauthors
Vlijm R,Lee M,Lipfert J,Lusser A,Dekker C,Dekker NHdoi
10.1016/j.celrep.2014.12.022subject
Has Abstractpub_date
2015-01-13 00:00:00pages
216-25issue
2issn
2211-1247pii
S2211-1247(14)01051-1journal_volume
10pub_type
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